Projects

Wenbo MuM.S, Bioinformatics

M.S, StatisticsB.S, Compute Sciences

•Analysis of Gene Expression

•Analysis of Genetic Variants

•Analysis of DNA Methylation

•Development of Data Mining Methods

Analysis Of Gene Expression

• Identified uniquely dys-regulated miRNAs in two types of colorectal cancer (MSI/MSS).

• Discovered fenfluramine-induced gene dys-regulation pattern in human pulmonary artery smooth muscle and endothelial cells.

• Explored distinct temporal involvement of microRNAs and pathways in lipopolysaccharide-induced acute lung injury in mice

Analysis Of Gene Expression---Quality Control

Box plot Clustering PCA

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Analysis Of Gene Expression---Analysis of mRNA Expression

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PASMC enriched GO Terms and Pathways

Yao W, Mu W*, Zeifman A, Lofti M, Remillard CV, Makino A, Garcia JGN, Yuan JX, Zhang W. Fenfluramine-induced gene dysregulation in normal human pulmonary artery smooth muscle and endothelial cells. Pulmonary Circulation. 2011; 1(3): 405-418. PMID: 22140631

GO term and Pathway AnalysisOverview of Differential Genes

Analysis Of Gene Expression---Functional Analysis

Network Analysis

Yao W, Mu W*, Zeifman A, Lofti M, Remillard CV, Makino A, Garcia JGN, Yuan JX, Zhang W. Fenfluramine-induced gene dysregulation in normal human pulmonary artery smooth muscle and endothelial cells. Pulmonary Circulation. 2011; 1(3): 405-418. PMID: 22140631

STK35

BMPR1B

ZFYVE16

TLL2

AMHR2

GDF10

Cytoscape

Analysis Of Gene Expression---Integrative Analysis of mRNA and microRNA

Integrated analysis to identify biologically-relevant miRNA/mRNA

Differential expression in CRC vs. normal

20#MSS#CRCs#

12#MSI#CRCs#

7#normal#mucosa#

miRNA/mRNA expression profiling

GeneChip® Human Gene 1.0 ST

(29k transcripts)

TaqMan® Human MicroRNA ‘A’

(377 microRNAs)

Samples

Identification of miRNAs and mRNAs differentially expressed between CRC and

normal mucosa

Prediction of mRNA targets according to miRNA expression

Identification of MSI-specific, MSS-specific, and pairs common to both

phenotypes (Table'1)

Selection of 10 highest ranked pairs (Figure'1): •  miRNA absolute fold change > 2.0

•  target mRNA greatest absolute fold change

Identification of inversely correlated mRNA/miRNA pairs within each CRC phenotype (MSI and MSS) 41#

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*Tumor# Normal#

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Xicola R, Mu W, Rawson J.B, Huang L, Sapoznik V.R, Doyle B.J, Jover R, Carracedo A, Andreu M, Bessa X, Castells A, Boland C.R, Goel A, Investigators E, Dai Y, Llor X. Identification of miRNAs and their gene targets differentially expressed in microsatellite stable and unstable colorectal cancers through an integrated analysis. Digestive Disease Week. 2011

Analysis Of Genetic Variants

• Preprocess Raw Data and Quality Control

• GWAS

• eQTL Identification

• Meta-analysis

• Admixture Mapping

• Genotype Imputation

Analysis Of Genetic Variants---Quality Control

Analysis Of Genetic Variants---GWAS

Analysis Of Genetic Variants---Imputation

Analysis Of Genetic Variants---Admixture Mapping

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Analysis Of DNA Methylation

• DNA methylation differentiation

• mQTL Identification

Analysis Of DNA Methylation---Quality Control

60#CEU#and#73#YRI#samples#

485,578&CpG#sites#

Illumina#450K#methyla=on#array#

1.#Remove#probes#whose#call#rate#<#0.95#2.#Remove#probes#that#map#ambiguously#to#the#genome#(~140,000)#3.#Remove#probes#that#contain#common#SNPs#[MAF>0.01]#(~55,000)#4.#Remove#probes#on#sex#chromosomes#(~7,000)#5.#Control#for#batch#effect#using#COMBAT#

283,540&highly#informa=ve##CpG#sites#

Extract#CpG#sites#by#gene#symbol#annota=on#Iden=fy#differen=al#methylated#probes#between#YRI#and#CEU#samples#using#Wilcoxon#Rank_sum#test#Evaluate#significance#of#methyla=on#enrichment#for#VIPs#using#fisher#exact#test##

135(24)&differen=ally#methylated#CpG#sites#

402&CpG#sites#within#43#VIPs#

Analysis Of DNA Methylation---mQTL Identification

Analysis Of DNA Methylation---mQTL Identification

Sample Codes---eQTL Identification

Development Of Data Mining Method

Development Of Data Mining MethodmRNA

expression miRNA

expression miRNA target

prediction

Correlation coefficient matrices

TF binding similarity score matrix

miRNA binding score matrix

Score matrix Module

Identification algorithm

Transcription factor binding profile

Module miRNA set

TF set Gene set

Mu W, Roqueiro D, Yang D. A Local Genetic Algorithm for the Identification of Condition-Specific microRNA-Gene Modules. Special Issue on Computational Systems Biology

Development Of Data Mining Method

Histogram of Permutated Modules

p value: 0.0034

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Development Of Data Mining Method

SKILLS